Article source: 35 bucket WeChat public account
Profile: Shi Dayong, Shandong University, professor, doctoral supervisor, foreign academician of the Russian Academy of Natural Sciences, member of Shandong Association for Science and Technology; "Young Top-notch Talents" of the Ten Thousand Talents Program of the Organization Department of the CPC Central Committee, Taishan Scholars of Shandong Province, Winners of the Outstanding Youth Fund of Shandong Province, Young and Middle-aged Experts with Outstanding Contributions in Shandong Province, Outstanding Young Scholars of Aoshan Talents of the National Marine Laboratory, Experts of High-end Think Tanks in Shandong Province, and Top-notch Talents of Qingdao City.
In the depths of the vast blue ocean, the deep and stretching ocean world is like a natural code book that has not been fully revealed, hiding countless precious resources covered with pearls and dust. In the meantime, a wide variety of active substances with different functions await the eyes of scientists to unleash the power to change the world.
In recent years, the cross-integration of marine biology and medical science has given rise to a series of scientific and technological innovations, one of which is the extraction and refinement of unique substances with significant biological activity from the abundant marine biological resources. Among them, the scientific research team led by Professor Shi Dayong, with its excellent professionalism and unremitting efforts, has discovered the "key" to solve the problem of animal disease prevention and control in the vast ocean.
Picture: Shi Dayong and his research team Image source: Courtesy of the interviewee
For more than 20 years, he has been grinding a sword, concentrating on research and practice, and is determined to solve the problem of pig disease
Shi Dayong told 35 Dou that when he was studying for his doctorate in 2002, he began to get involved in the research of halogenated compounds, and has more than 20 years of experience and accumulation.
2020 is a key time node for Shi Dayong to make an important breakthrough.
In the fall of 2020, Shi Dayong led a team to use virtual high-throughput screening technology to screen antiviral active compounds. During this period, a compound showed excellent antiviral potential, especially against coronavirus, but due to the limited access to physical samples of the new coronavirus, the team adjusted its strategy to attack the coronavirus porcine epidemic diarrhea virus (PEDV), which causes porcine epidemic diarrhea disease. At the same time, the team conducted a test on the efficacy of natural onset in a veterinary drug factory in Weifang, and the results of the experiment were encouraging - the condition of the treated piglets improved rapidly in a short period of time, their appetite was restored, and their mental condition was greatly improved.
Data show that 1-2 doses can significantly improve diarrhoea symptoms, and the risk of death can be rapidly reduced in 2-3 hours. The results of the subsequent challenge test showed that the cure rate of pigs in the Halostop treatment group was as high as 100%, while all the pigs in the control untreated group died.
Figure: Highly stop the test results Image source: Courtesy of the interviewee
The results of the experiment greatly encouraged Shi Dayong. Subsequently, Shi Dayong led the team to take the initiative to connect with animal husbandry management departments at all levels, and extensively conducted drug preclinical verification trials for retail pig breeding groups. Experiments have proved that the drug not only showed excellent virus inhibition performance in the laboratory against porcine epidemic diarrhea virus, but also quickly and effectively curbed the spread of the epidemic in actual combat, effectively alleviated the emergency crisis of many farmers, and also built a solid foundation for follow-up R&D and promotion work.
"We conducted a drug treatment experiment on 560 naturally occurring diseased piglets in Shandong Province, and the cure rate of Hailizhu was close to 96% at the end of the trial." This undoubtedly brings revolutionary solutions and new hope to the pig industry, which is plagued by such diseases, in the context of a mortality rate of nearly 100% within 7 days of age after PEDV infection and no specific treatment drugs have been marketed in the world. Based on the previous results, the team carried out large-scale validation trials across the country, involving 52 locations from Guangzhou to Harbin and Shenyang, with a total of more than 13,000 diseased piglets. The results showed that the drug had a high cure rate and a good safety profile for porcine epidemic diarrhea.
"This gave us a lot of confidence, so we also spent our main energy on this and further developed it."
The antiviral drug developed by the team is named "Halostop", which has far-reaching implications. On the one hand, it reflects the team's deep roots in the field of marine medicine, and on the other hand, the name creatively combines the English words "HEAL" (cure) and "Health" (health), which not only ensures the uniqueness and registrability of the trademark, but also symbolizes the rapid and effective treatment of diseases such as porcine epidemic diarrhea. At the end of 2021, the "Highly Stop" trademark was successfully registered and brand operation was launched.
Picture: "Haili Stop" picture Image source: Courtesy of the interviewee
From economic animals to companion animals, new marine drugs are leading to a new era of animal disease prevention and control
For a long time, Shi Dayong's team has been focusing on the extraction, modification and synthesis of marine active substances, especially in the field of haloactive compounds. The initial work focused on the exploration of marine active natural product resources, and successfully extracted and isolated a number of halogenated compounds with anti-tumor, antiviral and anti-diabetic properties from seaweed.
In order to solve the problem of drug source caused by the scarcity of these characteristic compounds in nature, the team innovatively adopted synthesis methods and successfully solved the bottleneck problem of large-scale preparation of halogenated compounds with the help of chemical synthesis technologies such as electron rearrangement. Today, the team has crafted a solid bioactivity database of nearly 3,000 halogenated compounds, detailing the origin, preparation pathway, yield, structural profiling and biological activity performance of each compound.
"What we have built is not a virtual database, but a physical library with physical compound sample storage, and each compound has a corresponding physical sample."
As the research deepened, the team began to study the effects of halogenated compounds on other members of the coronavirus family, especially for feline infectious peritonitis virus (FIPV). The study found that the compound can effectively inhibit the target of coronavirus, 3CLPro, which suggests that it may have broad-spectrum inhibitory activity against a variety of coronaviruses, including the new coronavirus. After a series of in vitro and in vivo experiments, the compound has shown good efficacy in the treatment of feline FIPV, bringing a new dawn for the treatment of feline infectious peritonitis, which was once regarded as a terminal disease.
After treating thousands of naturally occurring cats, Shi Dayong's team has achieved a high cure rate of nearly 90%, which is more convenient for oral administration and shows better therapeutic effects than drugs under development on the market, such as 441 (remdesivir derivative).
Based on the above achievements, the team strategically laid out a comprehensive product pipeline and launched a series of brand extensions for different animal markets, such as "Haili Meow" and "Haili Wang", which are dedicated brands for cats and dogs.
So far, Shi Dayong's team has obtained nearly 40 Chinese patents, 4 US invention patents and 2 EU invention patents.
Focus on three major areas and be the "leader" of the industry with two key resource pools
Shi Dayong pointed out that the team has adopted a forward-looking layout in the field of animal disease prevention and control, mainly focusing on the research and development of special drugs for the prevention and control of animal coronavirus diseases. At present, the company's product pipeline mainly covers three major market segments: the "Halostop" series for porcine epidemic diarrhea, the "Halomeow" for feline infectious peritonitis, and the "Halowang" for canine coronavirus enteritis. In addition, the company is also involved in the prevention and control of avian coronavirus diseases, especially infectious bronchitis in chickens and ducks, and duck coronavirus enteritis.
The company has established two core resource libraries: one is the compound library, which reserves thousands of drug candidate molecules against the coronavirus, so as to facilitate rapid response and drug screening when new virus epidemics emerge; The other is the virus bank, which contains a variety of animal coronavirus samples, which is conducive to efficient screening and targeted research. Shi Dayong said that the research and development of antiviral drugs is full of challenges and uncertainties, and many breakthroughs often originate from accidental discoveries and then achieve through systematic research and development and optimization.
"Luckily, our team was able to spot and catch these serendipities."
At present, the company has made major breakthroughs in two products, "Highly Stop" (for porcine epidemic diarrhea) and "Highly Meow" (for feline infectious peritonitis), which are expected to enter the clinical stage before the end of this year and are expected to become the first fist products to be commercialized. Up to now, the company has formed a comprehensive patent cluster, and will continue to strengthen patent protection measures and applications.
Looking forward to the future, Shi Dayong's team will focus on the prevention and treatment of animal coronaviruses, focusing on the prevention and treatment of epidemic diarrhea in pigs, infectious peritonitis in cats, enteritis in ducks, infectious bronchitis in chickens, and even in cattle and sheep, mammals, birds and even marine mammals. The first product is expected to be brought to market within one to one and a half years after entering the clinical stage, i.e. roughly between 2025 and 2026.